Biotransformation of norgestimate in women.

The metabolism of norgestimate (ORF-10131; 14C-d-13-ethyl-17-acetoxy-18,19-dinor-17 alpha-pregn-4-en-20- yn -3-oxime) was studied in humans. Compound labeled with carbon-14 in the 17 alpha-ethynyl group was administered to four female subjects. An average of 46.8 percent of the administered radioactivity was excreted in the urine and 36.8 percent in the feces over a two-week collection period. About 12 percent of the urinary radioactivity represented freely extractable metabolites and another 57 percent consisted of extractable material released by enzyme hydrolysis. The ethynylated metabolites of norgestimate were separated from endogenous compounds and non- ethynylated metabolites by silver- sulfoethyl cellulose column chromatography. Metabolites were subsequently isolated by high performance liquid chromatography and thin layer chromatography. The identification of five urinary metabolites was accomplished by combined gas-liquid chromatography/mass spectrometry. These metabolites include norgestrel, 16 beta- hydroxynorgestrel , 2 alpha- hydroxynorgestrel , 3 alpha, 5 beta- tetrahydronorgestrel , and a fifth trihydroxylated metabolite of undetermined stereochemical configuration; 3,16-dihydroxy-5- tetrahydronorgestrel .